PHILIP A contact WOLF

..Identification of persons at heightened risk for stroke, mild cognitive impairment, Alzheimer disease, and cognitive decline years prior to disease onset may facilitate delay in disease onset and prevention...

..We conducted a genome-wide association study (GWAS) for SCA measurements in the community-based Framingham Heart Study...

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..Prior investigations have reported several single gene variants associated with CHD, stroke, HF, and AF. We report a community-based genome-wide association study of major CVD outcomes...

..Genome-wide association studies (GWAS) provide mechanisms to investigate the genetic contributions to biomarker variability unconstrained by current knowledge of physiological relations...

..We conducted a genome-wide association (GWA) and linkage analysis exploring the genetic basis of these endophenotypes in a community-based sample...

..The impact of atrial fibrillation (AF) on mortality, stroke, and medical costs is unknown...

..We hypothesized that mid-life obesity may modulate the impact of conventional cardiovascular risk factors (CVRF) on cognitive impairment. We tested this hypothesis in the community-based Framingham Offspring Study sample...

..CONCLUSIONS: Elevated serum concentrations of aCLs, independently of other cardiovascular risk factors, significantly predict the risk of future ischemic stroke and TIA in women but not in men...

..To determine the independent effects of obesity on cognitive performance and to examine interactions between obesity and non-insulin dependent diabetes mellitus (NIDDM)...

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..This study sought to examine whether depressive symptoms are associated with an increased risk of cerebrovascular events in a community-based sample...

..We sought to examine whether epsilon(4) allele of the apoE gene influences the association between alcohol consumption and ischemic stroke or high-density lipoprotein (HDL) cholesterol...

..The lifetime risk (LTR) of stroke has not been reported for the United States population; such data would assist public education and health planning...

..Studies of newly diagnosed dementia are required in order to establish whether the elevated homocysteine levels precede the onset of dementia or result from dementia-related nutritional and vitamin deficiencies...

..The relation of carotid atherosclerosis to cognitive impairment and MRI indices of ischemia and aging in midlife is less clear...

..The present report presents a single multivariable risk function that predicts risk of developing all CVD and of its constituents...

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..Stroke is emerging as a major public health problem for women, as it is for men. Controversy persists regarding gender differences in stroke incidence, severity, and poststroke disability...

..The aim of this study was to assess whether pericardial fat, intrathoracic fat, and visceral abdominal adipose tissue (VAT) are associated with the prevalence of cardiovascular disease (CVD)...

..97; 95% confidence interval, 0.90-1.05). CONCLUSION: In this large, population-based cohort, baseline and long-term average serum total cholesterol levels were not associated with the risk for incident AD...

..CONCLUSIONS: Metabolic syndrome is more prevalent than diabetes and a significant independent risk factor for stroke in people without diabetes. Prevention and control of MetS and its components are likely to reduce stroke incidence...

..We performed a genome-wide linkage analysis to identify chromosomal regions that may harbor genes influencing WMH in a family-based sample of the Framingham Heart Study...

..Dense AD pathology in area 19 is present in some cognitively intact subjects with preclinical AD. The unique metabolic, connectional, and vascular features of this region may confer enhanced vulnerability to neurodegeneration...

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..Docosahexaenoic acid (DHA) is an abundant fatty acid in the brain. In the diet, DHA is found mostly in fatty fish. The content of DHA has been shown to be decreased in the brain and plasma of patients with dementia...

..8% and 17.7% depending on age, ethnicity, presence of comorbidities, and imaging techniques. We document the prevalence and risk factors associated with SCI at midlife in the community-based Framingham sample...

..Elevated plasma total homocysteine (tHcy) levels have been associated with increased risk of dementia and stroke, but it is uncertain whether the mediating mechanisms are predominantly cellular, vascular, or both...

..The results of this study suggest that improved control of risk factors has lowered stroke incidence but emphasize the need for continued primary prevention efforts...

..Thus, the lifetime burden attributable to common neurological disease is immense...

..Prior research has suggested that delay or avoidance of cardiovascular disease and cardiovascular disease risk factors plays an important role in longevity...

..Clinical hypothyroidism and hyperthyroidism are recognized causes of reversible dementia, but previous studies relating thyrotropin levels to cognitive performance in clinically euthyroid persons have yielded inconsistent results...

..To examine whether midlife cardiovascular risk factors predict survival and survival free of major comorbidities to the age of 85...

..Stroke is a major cause of death in the United States. The association between alcohol consumption and ischemic stroke (IS) remains controversial...

..Improved accuracy in the clinical diagnosis of AD is anticipated with the addition of molecular and structural biomarkers in the next generation of epidemiological studies...

..We hypothesized that cardiac function, as measured by cardiac index, would be associated with preclinical brain magnetic resonance imaging (MRI) and neuropsychological markers of ischemia and Alzheimer disease in the community...

..Genome-wide association studies (GWAS) have recently identified CLU, PICALM, and CR1 as novel genes for late-onset Alzheimer disease (AD)...

..We are currently performing analyses of data collected through 2002, and we discuss the statistical issues arising relating brain structure parameters to cognitive function...

..To investigate the relationship between a heart-healthy dietary pattern and subclinical heart disease in women, and to identify potential opportunities for primary prevention...

..Data relating parental history of stroke to stroke risk in offspring remain surprisingly inconsistent, largely because of heterogeneity of study design and the absence of verified, as opposed to historical, data on parental stroke status...

..We sought to test whether carotid IMT is associated with polymorphisms in several well-characterized genes in the hemostatic factor pathways...

..In conclusion, our data indicate little association between long-term moderate alcohol consumption and the risk of AF, but a significantly increased risk of AF among subjects consuming >36 g/day (approximatively >3 drinks/day)...

..We simultaneously assessed the relation of white matter hyperintensities and BI with incident stroke, mild cognitive impairment, dementia, and mortality in a middle-aged community-based cohort...

..We performed meta-analysis of genome-wide association studies of white participants in 6 studies comprising the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium...

..These data extend current knowledge by showing that these 2 different types of magnetic resonance imaging measures do not share underlying genetic or environmental influences...

..73). We investigated heritability of WMH in a family-based sample of the Framingham Heart Study for sex differences and the impact of age...

..These findings suggest that continued surveillance of each generation is necessary to document the impact that unique social and economic variables have on cognitive function. Here, the authors provide updated normative data...

..We hypothesized that plasma ADMA concentrations are positively related to common carotid artery intimal-media thickness (CCA-IMT) and to internal carotid (ICA)/bulb IMT...

..19; P = 2.3 x 10(-7)). We replicated this association in an independent cohort from the German AF Network (odds ratio = 1.44; P = 1.6 x 10(-11); combined RR = 1.25; combined P = 1.8 x 10(-15))...

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..To examine whether there are sex-specific associations between brain magnetic resonance imaging (MRI) measures and neuropsychologic (NP) test performance...

..Finally, the use of this unique sample to study genotype and environment interactions is described...

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..This study investigated the association of WMH and cognition in an ethnic and racial minority cohort (Omni) of the Framingham Heart Study and compared these results to the Caucasian (Offspring) cohort...

..We sought to relate circulating biomarkers of extracellular matrix turnover to site-specific measures of carotid artery atherosclerosis on duplex ultrasound...

..APOA5 variants were associated with CCA IMT, particularly in obese participants. The mechanism of these associations and the effect modification by obesity are independent of fasting triglyceride levels...

..Early preventive interventions may be important, because the inverse association between tHcy and cognitive performance is observed beyond middle age...

..Biomarkers of multiple pathophysiological pathways have been related to incident atrial fibrillation (AF), but their predictive ability remains controversial...

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..The relation of plasma ADMA to subclinical vascular brain injury has not been previously studied in a middle-aged, community-based sample...

..4; 95% CI: 1.5 to 3.9). CONCLUSIONS: Stroke increases a subject's risk of dementia as compared with age- and sex-matched controls. Primary and secondary prevention of stroke should significantly decrease the risk of all dementia...

..Bone mineral density (BMD) is a potential surrogate marker for cumulative estrogen exposure and has been associated with cognitive performance and risk of cognitive deterioration...

..Mobility limitation is associated with increased morbidity and mortality. The relationship between circulating testosterone and mobility limitation and physical performance is incompletely understood...

..Further study will clarify whether large WMH volume and associated cognitive impairment lead to future risk of stroke or dementia...

..Excess risk was apparent at natriuretic peptide levels well below current thresholds used to diagnose heart failure...

..Early-onset parental CHD, in particular, identifies offspring with a strong familial predisposition to atherosclerosis...

..CONCLUSION: These risk scores can be used to estimate the absolute risk of an adverse event in individuals with AF, which may be helpful in counseling patients and making treatment decisions...

..93 [1.15-3.24]). In our community-based sample, individuals with MetS have a high prevalence of subclinical atherosclerosis that likely contributes to the increased risk of overt CVD associated with the condition...

..Additional studies addressing the pathogenesis, prevention, and optimal management of the joint occurrence of AF and CHF appear warranted...

..Thus, in our elderly community-based sample, increased VTI E/A and a low atrial filling fraction were markers of increased risk of AF, suggesting that altered atrial filling may antedate AF...

..Further studies of genetic linkage and candidate gene association are warranted to identify specific genetic variants predisposing to subclinical atherosclerosis and stroke...

..CONCLUSIONS: There is a graded association between CRP and carotid atherosclerosis in women but not in men. The significance of this difference between sexes merits further investigation...

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..CONCLUSIONS: There is a low prevalence of CMBs in the community and a strong relationship with increasing age and male sex. We found no independent relationships with cardiovascular risk factors, APOE status, brain volumes, or WMH...

..Atrial fibrillation (AF) is the most common cardiac dysrhythmia and a source of considerable morbidity and mortality, but lifetime risk for AF has not been estimated...

..In conclusion, in a community-based sample, correlations among subclinical atherosclerosis test results are low, and a substantial proportion has high levels of subclinical atherosclerosis detected on >or=2 imaging tests...

..AAC appears to be useful for risk stratification in patients at intermediate CHD risk...

..However, few studies have investigated the association of walking speed with risk of incident ischemic stroke...

..The purpose of this study was to examine the link between LTL and the predisposition to atherosclerosis, as determined by carotid artery intimal medial thickness (IMT) in participants of the Framingham Offspring Study...

..28-17.72; P = .02). CONCLUSION: Diabetes mellitus did not increase the risk of incident AD in the Framingham cohort overall; however, DM may be a risk factor for AD in the absence of other known major AD risk factors...

..These results suggest that common genetic factors underlie longitudinal EF task performance. Genetic influences on EF decline, however, appear to be evident at longer time intervals between assessments...

..There is evidence that drinking large amounts of alcohol is related to brain atrophy. It is uncertain what the effects of low to moderate consumption might be...

..Lifetime risk for atherosclerotic cardiovascular disease (CVD) has not previously been estimated, and the effect of risk factor burden on lifetime risk is unknown...

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..The excess risk of AF associated with obesity appears to be mediated by left atrial dilatation. These prospective data raise the possibility that interventions to promote normal weight may reduce the population burden of AF...

..61), but participants using warfarin were younger. A total of 65 participants (17%) had major bleeding complications <or=5 years after initial AF. Age was not a significant predictor of bleeding...

..Our purpose was to compare the 20-year incidence of hospitalized stroke between Japanese-American men in the Honolulu Heart Program and white men in the Framingham Study...

..The purpose of this risk score is to accurately identify high-risk persons for enrollment in preventive and treatment trials. ..

..We will also be in a unique position to relate precursors of, and prior cardiovascular disease to dementia including vascular dementia and to determine the contribution of vascular factors to the dementia of AD. ..

..Until now only educated guesses among possible candidate genes for stroke risk were possible, these studies prioritize the recognized candidates and to identify new loci. ..

..We will perform genetic linkage analyses for MRI and cognitive performance measures in order to identify regions of the genome containing genes predisposing to AD and dementia. ..

..Since control of CVRF clearly prevents clinical stroke, it is hoped that data from this study will encourage control of CVRF and reduce the likelihood of cognitive decline and dementia. ..

..Understanding these interactions will advance our ability to formulate strategies to prevent stroke and minimize disability resulting from stroke. ..

..We will relate these data to previously measured risk factors and biomarkers already available on these subjects to determine a "pre-MCI" continuum of structural and functional indices of AD and dementia. ..

..Understanding these interactions will advance our ability to formulate strategies to prevent stroke and minimize disability resulting from stroke. ..

..And if so, do these risk factors promote AD via a nonvascular mechanism or "add" to brain injury thereby leading to earlier age of onset and/or accelerated. ..

..We will relate these data to previously measured risk factors and biomarkers already available on these subjects to determine a "pre-MCI" continuum of structural and functional indices of AD and dementia. ..

..Clinical and subclinical stroke in the Offspring will be related to documented stroke in parents and siblings to assess the impact of stroke risk factors depending on family history of stroke. ..

..Since control of CVRF clearly prevents clinical stroke, it is hoped that data from this study will encourage control of CVRF and reduce the likelihood of cognitive decline and dementia. ..

..And if so, do these risk factors promote AD via a nonvascular mechanism or "add" to brain injury thereby leading to earlier age of onset and/or accelerated. ..

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..Lastly, examination of noninvasive carotid and cardiac functional measures will be related to subsequent occurrence, type and severity of stroke...

..The decline in mortality rates from stroke has accelerated in recent years. Secular trends in incidence by stroke type will require more cases occurring over time and should be available as a by product of this proposal...